代谢
华法林是一种广泛用于治疗和预防血栓、慢性房颤、机械瓣膜、肺栓塞和扩张型心肌病的抗凝剂。它无味无色,曾被用作毒药,并且仍然作为针对老鼠的杀虫剂销售。几种长效华法林衍生物-超级华法林抗凝剂,如溴敌鼠、双苯丙酮、氯鼠灵、溴敌隆等,被用作杀虫剂,并能产生深刻和持久的抗凝作用。有几个因素会增加华法林中毒的风险。然而,细胞色素P450基因的多态性和药物相互作用是导致毒性并发症风险的主要原因。每个人对有毒物质的易感程度都是独特的。大多数有毒物质的毒性解释和健康风险是一个不确定性的主题。个体基因决定的低代谢能力可以显著改变毒素和代谢物水平,对于治疗指数狭窄的药物(如华法林)至关重要。个性化的解释方法有可能消除毒性案例中的一些科学不确定性。
Warfarin is a widely used anticoagulant in the treatment and prevention of thrombosis, in the treatment for chronic atrial fibrillation, mechanical valves, pulmonary embolism, and dilated cardiomyopathy. It is tasteless and colorless, was used as a poison, and is still marketed as a pesticide against rats and mice. Several long-acting warfarin derivatives-superwarfarin anticoagulants-such as brodifacoum, diphenadione, chlorophacinone, bromadiolone, are used as pesticides and can produce profound and prolonged anticoagulation. Several factors increase the risk of warfarin toxicity. However, polymorphisms in cytochrome P450 genes and drug interactions account for most of the risk for toxicity complications. Each person is unique in their degree of susceptibility to toxic agents. The toxicity interpretation and the health risk of most toxic substances are a subject of uncertainty. Genetically determined low metabolic capacity in an individual can dramatically alter the toxin and metabolite levels from those normally expected, which is crucial for drugs with a narrow therapeutic index, like warfarin. Personalized approaches in interpretation have the potential to remove some of the scientific uncertainties in toxicity cases.
来源:Hazardous Substances Data Bank (HSDB)